By correlating the antigenic expression on fetal lymphoid cells with the phenotypic determinant on malignant lymphocytes, we will establish the stage during differentiation at which leukocytes are susceptible to carcinogenic agents. Malignant transformation has been considered an arrest in cell differentiation. Thus, a characterization of neoplastic leukocytes will provide information to determine at what particular stage of normal leukocyte differentiation the neoplastic event occurred. We have thus far focused our attention on the development of B cells in the fetal liver. We have examined human fetal liver at various stages of gestation for the presence of B cells using antibodies to immunoglobulin isotypes and monoclonal B-cells, antibodies, which define B cells at different stages of development or activation. Our results show that the heterologous and monoclonal reagents can identify B-cell subsets as early as 12 to 13 weeks gestation. Furthermore, double staining methods developed in this laboratory have identified the B and pre-B cells as bearing the BA-1 and the mu-heavy chain. Only later, 14 to 16 weeks gestation, is the B-1 antigen expressed. We will begin to: (1)\examine the fetal liver pre-B cells for expression of tumor associated antigens; (2)\assay leukemias and lymphomas for similar phenotypic patterns; and (3)\analyze other fetal lymphoid organs for pre-B and B cell subpopulations. This study will contribute to the basic understanding of the origin of malignancy by identifying the susceptible stage during leukocyte differentiation at which a carcinogenic event has occurred and determine prognosis and treatment, since the course of disease and selection of therapy can be determined by the extent of cell maturation. (MI)